1. Field of the Invention
The invention concerns a process for producing a three-dimensional bioartificial tissue having viable cells in or on a matrix, and by which cells and matrix can be cultivated into a tissue or a precursor of a tissue, a vascularized tissue of biological materials, obtained by this process, and an experimental reactor for scientific purposes and for producing clinically usable tissues and organs.
2. Background Description
Bioartificial tissues are understood to be tissues produced in vitro from natural biological materials, which are, therefore, not natural tissues, but tissues which as nearly as possible simulate natural tissues.
The process according to the invention and the matching reactor are particularly suitable for producing a bioartificial heart muscle tissue.
Morbidity and mortality in the Western population are largely related to loss of heart function and heart tissue (cardiac failure). This is a problem of great socioeconomic relevance. Bypass surgery or heart transplants are increasingly necessary as ultimate therapeutic measures. Transplants, though, involve problems such as lack of suitable donor organs or the stress on transplant patients by lifelong treatment to suppress rejection reactions.
The problems of transplantation affect not only hearts, but also other organs which are no longer functional and which must be replaced. Because of these problems, major attempts have been made in medical research in the areas of “tissue retention” and “tissue and organ replacement”. Research endeavors on “tissue and organ replacement” comprise use and better adaptation of xenogeneic organs as well as the culture of three-dimensional tissues from natural starting materials so as to be able to replace at least parts of organs.
In the past, early cellular forms (e.g., embryonal stem cells or infant heart cells) have been injected into recipient myocardium (individually and as clumps of cells).
Prototypes of rat heart muscles in collagen, enriched with nutrients and growth factors have been made to produce, or, initially, to simulate, heart muscle from simple biological basic materials. Contractions have already been demonstrated with them. However, these experiments have not dealt with functional three-dimensional tissue which would be suitable for transplantation and which could replace damaged organ tissue (R. L. Carrier et al., “Cardiac Tissue Engineering: Cell Seeding, Cultivation Parameters and Tissue Construct Characterization”, Biotechn. Bioengin. 64 (5), 580-90, 1999).
The artificial pieces of heart tissue so obtained were only a few millimeters thick and never survived longer than a few weeks. After implantation, they were unable to integrate themselves into the recipient tissue so as significantly to improve the strength of beating (B. S. Kim et al., “Optimizing Seeding and Culture Methods to Engineer Smooth Muscle Tissue on Biodegradable Polymer Matrices”, Biotechn. Bioengin. 57 (1), 1998; R. K. Li et al., “In vivo Survival and Function of Transplanted Rat Cardiomyocytes”, Circ. Res. 1996; 78: 283-288). Thus the objective of the invention is to provide a process for producing an improved three-dimensional bioartificial tissue. In particular, vascularization of the tissue is attempted, so that it can be supplied and thus maintained in a viable state.